Bariatric surgery is the only treatment to date that induces large sustained weight loss and reduces obesity comorbidities and premature death, but emerging evidence indicates that it is also associated with increased risk of serious adverse events such as suicide and neonatal death. At present, the most widely used selection criteria for bariatric surgery are based on strict BMI cutoffs, but there is increasing awareness that we need to improve our identification of who will benefit most from surgery, both in terms of health outcomes and economic costs. Our overall goal is to use large register-enriched Swedish patient cohorts to determine the health benefits, risks, and economic costs of bariatric surgery, and to use this information to improve prediction of treatment success. We will use register-enriched data from: (1) the SOS study cohort comprising 2010 surgically treated patients and 2037 matched controls; and (2) a newly established clinical cohort (SOReg/Itrim) of more than 60,000 patients who either underwent bariatric surgery or received low or very low calorie diets, and includes understudied populations (pregnant women, adolescents, the elderly, patients with BMI<35/<40). Virtually complete follow-up of risks, benefits and health economic outcomes until death or emigration is possible through Swedish nationwide and mandatory registers, allowing for unbiased analyses. Our cohorts also have the advantage of long follow-up (up to 27 years for SOS and 8 years for SOReg/Itrim), and include control groups who receive standard or intensive non-surgical obesity care. Our specific aims are: (1) to determine the health benefits of bariatric surgery over up to 27 years of follow-up (including overall and cause-specific mortality; heart diseases; and micro- /macrovascular disease risk in patients without diabetes at baseline); (2) to determine specific risks of bariatric surgery over up to 27 years of follow-up (including suicide, self-harm, and substance abuse; neonatal death in post-bariatric surgery pregnancies; and fractures); (3) to estimate the economic consequences of bariatric surgery (in subgroups divided by baseline glucose status and understudied populations); and (4) to identify predictors of treatment success for improved patient selection (in terms of both overall health effects and incremental cost- effectiveness). The results of our research will resolve uncertainties surrounding the long-term health benefits, risks, and economic outcomes of bariatric surgery. By analyzing data from specific patient subgroups and understudied populations, our results will provide unique information on the risk- benefit ratio and incremental cost-effectiveness ratio for bariatric surgery overall and in certain patient segments. We anticipate that our results will contribute to improved patient selection and influence change of the outdated BMI-based eligibility criteria for bariatric surgery.